Advertisement

Archives of Toxicology

, Volume 61, Issue 4, pp 249–258 | Cite as

The genotoxicity of trenbolone, a synthetic steroid

  • Margaret Richold
Original Investigations

Abstract

Trenbolone, a synthetic androgen is used as a growth promotant in animal husbandry. Because of its steroidal structure and properties it has been extensively evaluated in a series of in vitro and in vivo assays to assess its genotoxic and initiating properties. Both the parent molecule 17-beta-hydroxytrenbolone and its metabolite 17-alpha-hydroxytrenbolone, produced only in cattle, have been tested. 17-beta-hydroxy-trenbolone was not genotoxic in the Ames Salmonella/microsome assay, cytogenetics assays in human lymphocytes and CHO cells, a micronu cleus assay in CHO cells, a DNA repair synthesis assay in HeLa cells, mammalian cell mutation assays with CHO and V79 cells, the mouse micronucleus assay, rat bone marrow or spermatogonial cytogenetics assays or in a test for initiators in the rat. In the mouse lymphoma cell mutation assay with L 5178Y Tk±cells, equivocal responses were obtained, particularly at highly toxic concentrations. With 17-alpha-hydroxytrenbolone a weak positive response was obtained in the L5178Y Tk±assay, particularly at highly toxic concentrations. Negative results were obtained in the Ames Salmonella/microsome assay, the cytogenetics assays using both human lymphocytes in vitro and rat bone marrow in vivo, the DNA repair assay and in the CHO mammalian cell mutation assay. It was also negative in the in vivo test for initiators. From this extensive battery of data, and also taking into account published data on trenbolone, it is concluded that 17-alpha-hydroxytrenbolone and 17-beta-hydroxy-trenbolone are devoid of genotoxic activity and are not initiators of cancer.

Key words

Trenbolone Genotoxicity Hormones Synthetic hormones Mammalian cells 

Abbreviations

β-TBOH

17-beta-hydroxy-4,9,11-androstatrien-3-one

α-TBOH

17-alpha-hydroxy-4,9,11-androstatrien-3-one

DES

diethylstilboestrol

TFT

triflurothymidine

UDS

unscheduled DNA synthesis

SHE

Syrian hamster embryo

DMSO

dimethylsulphoxide

6TG

6-thioguanine

PHA

phytomaemagglutinin

CHO

Chinese hamster ovary cells

V79

Chinese hamster lung cells

HPRT

hypoxanthine-guanine phosphoribosyl transferase

2-AAF

2-acetylaminofluorene

20 MC

20-methylcholanthrene

Mit C

mitomycin C

EMS

ethylmethane sulphonate

DEN

diethylnitrosamine

Oestrad

oestradiol

Nitrosomorph

nitrosomorpholine

ethinyl oestr

ethinyl oestradiol

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amacher DE, Paillet S, Ray V (1979) Point mutation at the thymidine kinase locus in L5178Y mouse lymphoma cells. Mutat Res 64: 391–406Google Scholar
  2. Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res 31: 347–364Google Scholar
  3. Ashby J (1983) The distinction between genetic and non-genetic mechanisms in chemical carcinogenesis. In: Zbinden et al. (eds) Current problems in drug toxicology. John Libby Eurotext, Paris LondonGoogle Scholar
  4. Ashby J (1982) Hormones, cancer and short-term genotoxicity data. European Toxicity Forum Meeting, Geneva May 3–7, 1982, pp 339–346Google Scholar
  5. Banduhn N, Obe G (1985) Mutagenicity of 2-benzimidazolecarbamate, diethylstilboestrol and oestradiol: Structural chromosomal aberrations, sister-chromatid exchanges, C-mitosis, polyploidies and micronuclei. Mutat Res 156: 199–218Google Scholar
  6. Barraud B, Lugnier A, Dirheimer G (1983) In vivo covalent binding to rat liver of trenbolone as compared to 17β-oestradiol, testosterone and zeranol. In: Meissonnier (ed) Anabolics in human production. Soregraph, France, pp 325–338Google Scholar
  7. Bradley MO, Bhuygan B, Francis MC, Lanagenbach R, Peterson A, Huberman E (1981) Mutagenesis by chemical agents in V79 Chinese hamster cells. Mutat Res 87: 81–142Google Scholar
  8. Clive D, Spector JFS (1975) Laboratory procedure for assessing specific locus mutations at the Tk locus in cultured L 5178Y mouse lymphoma cells. Mutat Res 31: 17–29Google Scholar
  9. Drevron C, Picoli C, Montesano R (1981) Mutagenicity assays of oestrogenic hormones in mammalian cells. Mutat Res 89: 83–90Google Scholar
  10. Evans HJ, O'Riordan (1975) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. Mutat Res 31: 135–148Google Scholar
  11. Heddle JA (1983) The induction of micronuclei as a measure of genotoxicity. A report of the US Environmental Protection Agency Gene-Tox Program. Mutat Res 123: 61–118Google Scholar
  12. Helton Ed, Casciano DA, Althaus ZR, Plant HD (1977) Metabolism of 17β-ethynylestradiol by intact liver parenchymal cells isolated from mouse and rat. J Toxicol Environ Health 3: 953–963Google Scholar
  13. Hsie AW, Casciano DA, Couch DB, Krahn DF, O'Neill JP, Whitefield BL (1981) The use of Chinese hamster ovary cells to quantify specific locus mutation and to determine mutagenicity of chemicals. A report of the gene-tox program. Mutat Res 86: 193–214Google Scholar
  14. Lang R, Redmann U (1979) Non-mutagenicity of some sex hormones in the Ames Salmonella/microsome mutagenicity test. Mutat Res 67: 361–365Google Scholar
  15. Lutz WK, Caviezel M, Marinovich M, Friederich U, Schlatter C (1985) Investigation of mutagenicity and of the potential for binding of trenbolone to DNA in rat liver in vitro. Abstract, German Cancer Society, March 6–8 1985, HeidelbergGoogle Scholar
  16. Martin CN, McDermid AC, Garner RC (1978) Testing of known carcinogens and non-carcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res 38: 2621–2627Google Scholar
  17. Matter B, Schmid W (1976) Trenimon- induced chromosomal damage in bone marrow cells of six mamalian species, evaluated by the micronucleus test. Mutat Res 12: 417–425Google Scholar
  18. Rogers AW (1973) Techniques in autoradiography. Elsevier, AmsterdamGoogle Scholar
  19. Ruttenberg AM, Kim H, Fischbein JW, Hanssker JS, Wasserkrug HL, Seligman AM (1968) Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity. J Histochem Cytochem 17: 517–526Google Scholar
  20. Scheutwinkel M, Hude W v d, Bassler A (1986) Studies on the genotoxicity of the anabolic drugs trenbolone and zeranol. Arch Toxicol 59: 4–6Google Scholar
  21. Schiffmann D, Metzler M, Neudecker T, Henschler D (1985) Morphological transformation of Syrian hamster embryo fibroblasts by the anabolic agent trenbolone. Arch Toxicol 58: 59–63Google Scholar
  22. Schuppler J, Damme J, Schulte-Hermann R (1983) Assay of some endogenous and sex steroids for tumor-initiating activity in the rat liver using the Solt-Farber system. Carcinogenesis 4: 239–241Google Scholar
  23. Solt D, Farber E (1976) New principle for the analysis of chemical carcinogenesis. Nature 263: 701–703Google Scholar
  24. Stich HF, San RHC, Kawazoe Y (1971) DNA repair synthesis in mammalian cells exposed to a series of oncogenic and nononcogenic derivatives of 4-nitroquinoline oxide. Nature 229: 416–419Google Scholar
  25. White AD (1980) In vitro induction of SCE in human lymphocytes by epichlorohydrin with and without metabolic activation. Mutat Res 78: 171–176Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Margaret Richold
    • 1
  1. 1.Huntingdon Research CentreHuntingdonEngland

Personalised recommendations